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The macrophage activation marker sCD 163 is associated with morphological disease stages in patients with non‐alcoholic fatty liver disease
Author(s) -
Kazankov Konstantin,
Barrera Francisco,
Møller Holger Jon,
Rosso Chiara,
Bugianesi Elisabetta,
David Ezio,
Ibrahim Kamal Jouness Ramy,
Esmaili Saeed,
Eslam Mohammed,
McLeod Duncan,
Bibby Bo Martin,
Vilstrup Hendrik,
George Jacob,
Grønbæk Henning
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.13150
Subject(s) - fatty liver , disease , macrophage , alcoholic liver disease , pathogenesis , medicine , pathology , biology , biochemistry , cirrhosis , in vitro
Background & Aims Macrophage activation plays a key pathogenic role in experimental non‐alcoholic fatty liver disease ( NAFLD ) and contributes to the progression of steatohepatitis ( NASH ) and fibrosis. We studied macrophage activation in human NAFLD by measuring soluble (s) CD 163, a specific macrophage activation marker, hypothesizing that sCD 163 would be associated with the patients’ morphological disease grade. Furthermore, we investigated an association between sCD 163 and the apoptosis marker cytokeratin‐18 ( CK ‐18) to explore a link between macrophage activation and apoptosis. Methods sCD 163 associations with biochemical and histological measures of NAFLD were investigated in two independent cohorts of 157 Australian and 174 Italian NAFLD patients, with liver biopsies graded for NAFLD severity, steatosis and fibrosis. sCD 163 and CK ‐18 were measured by enzyme‐linked immunosorbent assay. Results In both cohorts sCD 163 increased in parallel with the patients’ morphological disease grading, being independently associated with the Kleiner fibrosis score ( P < 0.001). A high sCD 163 predicted advanced fibrosis {F ≥ 3; Australian cohort: area under receiver‐operating characteristics curve 0.77 [95% confidence interval ( CI ): 0.76–0.87], Italian cohort: 0.80 (95% CI : 0.72–0.88)}. In both groups, sCD 163 was independently associated with CK ‐18 ( P < 0.001). Conclusion Soluble CD 163 reflecting macrophage activation is associated with morphological features of NAFLD suggesting their involvement in the pathogenesis of NAFLD , NASH and particularly fibrosis. An independent association between sCD 163 and cytokeratin‐18 suggests that apoptosis may contribute to macrophage activation in NAFLD / NASH .